Abstract | BACKGROUND: METHODS AND RESULTS: Rat hearts were transfected with human HSP72 by intra-coronary infusion of Hemagglutinating Virus of Japan- liposome, resulting in global myocardial overexpression of HSP72. After ischemia-reperfusion injury, cardiac function (left ventricular systolic pressure, maximum dP/dt, minimum dP/dt, and coronary flow) was improved in the HSP72-transfected hearts compared with control-transfected ones, corresponding with less leakage of creatine kinase and mitochondrial aspartate aminotransferase. Postischemic Mn-SOD content and activity in the HSP72-transfected hearts were enhanced in comparison with the controls (content: 96.9+/-4.1 versus 85.5+/-2.5% to the preischemic level, P=0.038; activity: 93.9+/-2.2 versus 82.2+/-3.7%, P=0.022), associated with improved mitochondrial respiratory function (postischemic percent respiratory control index; NAD(+)-linked: 81.3+/-3.8 versus 18.5+/-4.4%; FAD-linked: 71.8+/-5.5 versus 20.7+/-5.3%, P<0.001). In addition, incidence of postischemic cardiomyocyte apoptosis was attenuated in the HSP72-transfected hearts (4.0+/-1.1 versus 10.3+/-3.3%, P=0.036), correlating with an increased Bcl-2 level and reduced up-regulation of caspase-3. CONCLUSIONS: These data suggest that the enhanced Mn-SOD activity during ischemia-reperfusion injury, which is associated with mitochondrial protection and apoptosis reduction, is a possible mechanism of HSP72-induced cardioprotection.
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Authors | Ken Suzuki, Bari Murtuza, Ivan A Sammut, Najma Latif, Jay Jayakumar, Ryszard T Smolenski, Yasufumi Kaneda, Yoshiki Sawa, Hikaru Matsuda, Magdi H Yacoub |
Journal | Circulation
(Circulation)
Vol. 106
Issue 12 Suppl 1
Pg. I270-6
(Sep 24 2002)
ISSN: 1524-4539 [Electronic] United States |
PMID | 12354745
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cardiotonic Agents
- HSP72 Heat-Shock Proteins
- Heat-Shock Proteins
- Superoxide Dismutase
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Topics |
- Animals
- Apoptosis
- Cardiotonic Agents
- Enzyme Activation
- HSP72 Heat-Shock Proteins
- Heart
(physiopathology)
- Heat-Shock Proteins
(genetics, physiology)
- Mitochondria
(physiology)
- Myocardial Reperfusion Injury
(enzymology, pathology, physiopathology)
- Myocardium
(enzymology, metabolism, pathology)
- Rats
- Rats, Inbred Lew
- Superoxide Dismutase
(metabolism)
- Transfection
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